DprE1 Inhibitors: An insight into the recent developments and synthetic approaches.

In the current medical era, the proliferation and dissemination of drug-resistant strains of Mycobacterium tuberculosis continue to pose a significant worldwide health hazard, necessitating the development of new and innovative medications to combat tuberculosis. Decaprenylphosphoryl-β-D-ribose 2'-epimerase (DprE1) is a crucial enzyme for cell wall synthesis in Mycobacterium tuberculosis (Mtb). Its importance is due to its eminent contribution in forming lipoarabinomannan and arabinogalactan. The emergence of the DprE1 enzyme as a druggable target was based on inhibitors discovered in high-throughput screening. Since then, inhibitors with different types of chemical scaffolds have been reported for their activity against it. DprE1 inhibitors can be categorized according to the formation of a covalent or non-covalent bond in the enzyme's active site, causing a loss of its catalytic activity, leading to Mtb's demise. Herein, we describe diverse DprE1 inhibitors that have had anti-tubercular activity reported over the past fifteen years and till the present time.